The specific aims of our original proposal, the Role of Activated B Lymphocytes in Immune responses were 1) to compare the function of activated and unactivated human B lymphocytes with regard to their capacity to interact with T lymphocytes; 2) to explore possible mechanisms of the augmented function of activated, compared with resting, B lymphocytes and 3) to examine the role of the B cell activation described in patients with SLE in the immunoregulatory defects noted in that disease. Data obtained over the past two years have elucidated the sequence of interactive events between T and B cells that results in helper T cell function and eventual Ig secretion. We have recently devised a rapid and sensitive assay which measures direct T helper (Th) cell - induced B cell activation as expression of an early B cell-restricted activation antigen, BLAST-2. We study the role of BLAST-2 in B cell differentiation. We plan of define the functional properties of the BLAST-2 molecule, to isolate and measure soluble BLAST-2 molecules; to study the mechanisms of Th cell-induced BLAST-2 expression, seeking a role for antigen- activated T cells and soluble factors in this activity; and to measure T cell-induced BLAST-2 expression and soluble BLAST-2 production in SLE and RA patients. We hope to elucidate the mechanisms of B cell activation and differentiation in normal subjects and to add to our understanding of the B cell hyperactivity characteristic of autoimmune disease.